1. Technical Field
The present invention relates to techniques for localization and measurement of the dynamics of neuronal activity associated with information processing in the brain, and more particularly to systems and methods for using sodium-23 magnetic resonance imaging to measure evoked neuronal activity in the brain.
2. Discussion
The pursuit of methods for measurement and 3-D localization of neuronal activity associated with information processing in the brain has inspired much research in electrophysiology, radiology, nuclear medicine, biophysics, scientific visualization, and other disciplines. Such methods provide important uses in many areas including basic research into the functioning of the brain; early diagnosis of brain diseases; and assessment of post-therapeutic and postoperative brain functions. Nevertheless, present day technologies still fall short of realizing these goals. There remains no satisfactory technique to visualize in 3-D the sequence of activation of brain nuclei and cortices during the processing of various sensory, motor, cognitive, and other tasks.
Current techniques for measurement of brain activity generally fall into two categories: direct and indirect measurement techniques. Direct approaches include Electroencephalography (EEG), Evoked Potentials (EP) and Magnetoencephalography (MEG). Indirect techniques include Positron Emission Tomography (PET) of glucose metabolism or Cerebral Blood Flow (CBF) and Single Photon Emission Computed Tomography (SPECT).
The direct techniques of EEG and EP are widely available and represent a relatively inexpensive technology for measurement of brain potentials. These techniques use scalp or depth implanted electrodes to acquire the signal. A major shortcoming is that they do not allow for unambiguous localization of the intra-cranial potential generators. Rather, scalp EEG/EP at best provide a temporal sequence of 2-D maps each of which represents the momentary spatial distribution of the brain potentials as they appear on the scald, whereas depth EEG/EP provide very localized measures of the potential in the vicinity of implanted electrodes. Magnetoencephalography (MEG) is a relatively new and expensive technology (systems may cost up to $3,000,000) for remote sensing (non-invasive measurement) of the magnetic fields associated with the electric currents produced during neuronal activity. MEG uses SQUID (Superconducting Quantum Interference Device) magnetometers to detect weak magnetic fields outside the brain.
EEG and MEG are complimentary since they measure two manifestations of the same physical phenomenon--the ionic currents underlying neuronal activity. (EEG measures the electric fields, whereas MEG measures the magnetic fields generated by these currents.) However, when used to determine the intracranial localization of field generators, both techniques require solving what is known as the "inverse problem". This is an ill-posed problem of reconstruction of the location and strength of the generators in the brain from data measured on the surface of the brain. The limitations with this method are: (1) current compartmental models make many simplifications about the dielectric properties of the brain which may compromise the accuracy of the solution; (2) even if there were accurate models, there is not a unique solution to the inverse problem. That is, any given scalp EP field distribution could theoretically be generated by an infinite variety of intracerebral source distributions.
The indirect techniques for observation of neuronal activation such as PET and SPECT have their own drawbacks: (1) these techniques have insufficient temporal resolution, which is at best in the range of 60 seconds; (2) these techniques measure indirect correlates of the neuronal activity, such as blood flow or glucose metabolism. These variable have dynamics which lag behind the neuronal activity which evoke them by at least 1 second or more. Also, the response is smeared in time and has non-linear relation to the underlying neuronal activity.
Besides the unsatisfactory results for localization of neuronal activity, all of the above techniques present additional disadvantages. For example, EEG and EP are invasive, since they require attachment or implantation of electrodes. PET and SPECT require the administration of radionucleotides (e.g., 18-FDG, 15-O water., IMP, 133-Xenon). Further, 3-D brain imaging has not been possible with the techniques of EEG and MEG. An additional disadvantage with techniques such as PET, SPECT and MEG is that they require a large investment in equipment thus posing a serious barrier to their widespread implementation.
Thus, it would be desirable to provide a system and method for simultaneously visualizing neuronal activity in all areas of the brain. Also, it would be desirable to provide a system and method for visualizing the sequence of activation of brain nuclei and cortices which underlie various sensory, motor, cognitive and other tasks. In addition, it would be desirable to provide such a technique which has sufficient temporal resolution to resolve rapidly changing neuronal activity. Further, it would be desirable to provide such a technique for localization of neuronal activation in the brain which directly measures this activity as opposed to measuring indirect correlates. It would also be desirable to provide such a technique which is not invasive and which does not require administering any substances into the brain. Further, it would be desirable to provide such a technique which provides sufficient spatial resolution to resolve fine spatial details within the brain. Also, it would be desirable to provide a technique with these features which produces brain images which are three-dimensional. Additionally, it would be desirable to provide such a system which can be implemented at a reasonable cost.